Short-Term Within-Host Genomic Diversity and Clone Turnover of Carbapenem-Resistant Klebsiella pneumoniae in an Intensive Care Unit Patient

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a critical public health threat because infections caused by this pathogen are associated with high morbidity, mortality, and limited effective therapeutic options. Whilst the majority of studies have concentrated on inter-patient bacterial transmission, within-host genomic analysis offers unprecedented resolution for tracking dynamic clone predominance, plasmid rearrangements, and microevolution under clinical selection pressures. Methods and Results: Whole-genome sequencing (WGS) of nine isolates recovered from oral and rectal swabs revealed an exceptional case of CRKP clonal turnover in an intensive care unit (ICU) patient. Three distinct high-risk clones were identified during the 18 days of surveillance: an initial ST101 (Clonal Group (CG) 101) strain (days 1–7) followed by concurrent colonization with ST395 (carrying blaNDM-5) and ST512 lineages (both CG258, days 11–18). Conclusions: This study describes a rare instance of within-host heterogeneity of CRKP, involving three distinct STs spanning two CGs. Whole-genome analysis revealed potential structural rearrangements of resistance- and virulence-associated plasmids between coexisting lineages. These genomic shifts likely reflect rapid adaptation under the intense selective pressure of broad-spectrum antibiotic therapy, culminating in the persistence of a less virulent yet multidrug-resistant ST512 clone and a favorable clinical outcome with patient recovery.